Case Study 58

Case Study 58
Kenneth Clark, MD
Question 1
• This is a 4-year-old boy with refractory epilepsy
attributable to the right temporal region. An MRI
as well as PET CT showed subtle changes in
the right temporal lobe consistent with the origin
of his seizures. He underwent an uncomplicated
right-sided grids placement for mapping of his
seizures. Several days later he returned to the
OR for removal of grids and for right-sided
temporal lobectomy.
• Describe the subtle MRI and PET findings.
Axial T1
Axial T1 + Contrast
Axial T2 FLAIR
• MRI - Increased T2 FLAIR signal in the cortex
and subcortical region of the superior gyrus of
the posterior right temporal lobe, minute cystic
areas in this same region. No discrete lesions or
areas of enhancement.
• PET CT - Diffuse hypometabolism involving the
entire right temporal lobe. Remaining cerebral
cortex, subcortical structures and the cerebellum
show no metabolic abnormalities.
Question 2
• What is the differential diagnosis of a temporal
lobe lesion in a child with epilepsy?
• Cortical Dysplasia
• Ganglioglioma
• Dysembryoplastic Neuroepithelial Tumor
• Xanthoastrocytoma
Question 3
• The lesion was resected. Describe the findings.
• Click here to view the slide
• The tissue shows a large segment of hypercellular grey
matter with predominantly small and irregularly shaped
neurons admixed with increased numbers of atypical
astrocytes and increased background vascularity. Within
this region of cortex and adjacent white matter are
multiple well-circumscribed glial nodules comprised of
oligodendroglia-like cells with small round nuclei and
perinuclear cytoplasmic clearings. The background
within the nodules shows rich thin-walled vascular
networks and rare entrapped neurons. The periphery of
the lesion shows foci of severe cortical dysplasia
including small regions with balloon cell change.
Question 4
• What is your diagnostic impression?
• Dysembryoplastic Neuroepithelial Tumor
(DNET), Complex Type
Question 5
• What additional immunohistochemical stains
would you order to better characterize this
• GFAP (glial elements)
• NeuN (neuronal elements)
• Synaptophysin (help characterize degree of
neuronal aberrancy in lesional cortex)
• Ki67 (proliferation index)
• Neurofilament (axonal pathology)
• Click to see GFAP, NeuN, Synaptophysin,
Neurofilament, Ki67
Question 6
• How would you describe the
immunohistochemical findings?
• GFAP - highlights astrocytic component of cortical
glioneuronal element; negative in glial nodules
• Synaptophysin - reduced staining within glioneuronal
region (compared to unaffected cortex); slight staining
within white matter
• NeuN - highlights small, round, dysplastic neurons and
effaced laminar structure in glioneuronal region; also
reveals scattered small neurons in white matter tracts;
negative in glial nodules
• Neurofilament - highlights white matter axons
• Ki67 - stains less than 1% of glioneuronal cells;
highlights numerous proliferating inflammatory cells &
macrophages near grid wire insertion tracts
Question 7
• Do these stains confirm your diagnosis? Explain.
• Yes. The NeuN staining highlights severe
neuronal cortical dysplasia within the
glioneuronal neoplastic element as well as
numerous scattered neurons in the subcortical
white matter. This is further confirmed by the
reduced synaptophysin staining in the affected
regions. Furthermore, the GFAP staining
highlights the glial component of the neoplasm
and absent staining of the oligodendroglial
nodules typify the complex DNET variant.
Question 8
• What grade is a dysembryoplastic
neuroepithelial tumor?
• DNETs, both classic and complex, are
considered WHO grade 1 lesions.
Question 9
• How often is cortical dysplasia found in
association with this tumor?
• Some studies have shown that cortical dysplasia
can be found in as many as 80% of DNETs.
Question 10
• What is the primary differential diagnosis with a
DNET? How would you make the distinction?
• The main differential with DNET is
ganglioglioma. They are both WHO grade 1
lesions with neoplastic neuronal elements.
• Similarities:
– Variable numbers of neoplastic ganglion cells
– Multinodular structures
– Very similar clinical presentations
• Differences:
– Gangliogliomas more often have large cystic
components than DNET.
– Gangliogliomas often have perivascular lymphocytic
infiltrates where DNETs do not.
– Gangliogliomas demonstrate a rich background of
reticulin fibers where DNETs do not.
Question 11
• Why is the distinction between DNET and
ganglioglioma important?
• Making the distinction between DNET and
ganglioglioma is important because
gangliogliomas can undergo malignant
transformation with anaplastic changes in the
glial component of the tumor (resembling high
grade glioma), whereas DNETs do not. This has
prognostic and follow-up implications.
• Louis D, Ohgaki H, Wiestler O, Cavanee W. WHO Classification of
Tumours of the Central Nervous System. IARC: Lyon 2007.
• Pasquier B, Peoch M, Fabre-Bocquentin B, Bensaadi L, Pasquier D,
Hoffmann D, Kahane P, Tassi L, Le Bas J, Benabid A. Surgical
pathology of drug resistant partial epilepsy. A 10-year-experience
with a series of 327 consecutive resections (2002). Epileptic
Disorders. 4:99-119.
• Prayson R, Khajavi K, Comair Y. Cortical architectural abnormalities
and MIB1 immunoreactivity in gangliogliomas: a study of 60 patients
with intracranial tumors (1995). Neuropathol Exp Neurol. 54:513520.
• Daumas-Duport C, Varlet P, Bacha S, Beuvon F, Cervera-Pierot P,
Chodkiewicz J. Dysembryoplastic neuroepithelial tumors: nonspecific histological forms – a study of 40 cases. J Neurooncol.